Project Summary/Abstract Barth syndrome (BTHS; OMIM #302060) is a rare, life-threatening, X-linked, multi-system genetic disorder affecting primarily males [1-6]. The cardinal characteristics of this unique mitochondrial disease are dilated cardiomyopathy (sometimes hypertrophic cardiomyopathy), muscle hypoplasia, extreme fatigue/weak- ness, neutropenia, growth delay, and a reduction of tetralinoleoyl cardiolipin (a major phospholipid of the mitochondrial inner membrane). In the first description of Barth syndrome in 1983, Dr. Barth delineated all of the principal clinical findings, established the X-linked mode of inheritance, and described the abnormalities of mitochondrial structure and function in muscle and leukocytes. In 1996 causative mutations for BTHS were found in the gene subsequently designated tafazzin or TAZ, located in the gene-rich Xq28 chromosomal region [7]. In 2000 Dr. Peter Vreken and colleagues discovered that fibroblasts from BTHS patients have essentially absent levels of mitochondrial tetralinoleoyl cardiolipin [8]. Fortunately, this discovery also coincided with the incorporation of the Barth Syndrome Foundation (BSF) as a non-profit, patient-advocacy group Since its inception in 2000 BSF has sponsored biennial International Scientific, Medical and Family Conferences (hereafter referred to as Conferences) to highlight scientific and clinical advances, to educate patients and their families, to help deal with patient concerns, to promote the advancement of BTHS research and researchers, and to establish a vibrant patient-centered community. These unique Conferences have evolved from simple gatherings of a few families who have sons suffering from this rare disease together with their treating physicians, to International Conferences where important scientific and clinical advancements are presented and new investigators to the field are recruited, encouraged, and supported. The search for therapeutic treatments or compounds is always a major focus of these Conferences. At the 2016 and 2018 Conferences, pharmaceutical clinical trials were discussed and now they have become part of the BSF experience. At the 2020 Conference we will hear updates and reports from the TAZPOWER trial in the US and the CARDIOMAN trial in the UK. In 2020 we expect to hear planning for a gene therapy trial, about enzyme replacement therapy, and about modifier gene therapy using ALCAT1 inhibitors. Besides the scientific advances communicated at these meetings these Conferences are the only forums where therapies and therapeutic ideas can be effectively presented, discussed, critically evaluated, and acted upon. This is vital to advance the field not only by the researchers and physicians directly involved, but also by the affected individuals and their families. These Conferences add value to science and medicine in general and provide real hope to BTHS individuals.